BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Pig large tumor suppressor 2 (Lats2), a novel gene that may regulate the fat reduction in adipocyte

  • Liu, Qiuyue (State Key Laboratory for Agrobiotechnology, China Agricultural University) ;
  • Gu, Xiaorong (State Key Laboratory for Agrobiotechnology, China Agricultural University) ;
  • Zhao, Yiqiang (State Key Laboratory for Agrobiotechnology, China Agricultural University) ;
  • Zhang, Jin (State Key Laboratory for Agrobiotechnology, China Agricultural University) ;
  • Zhao, Yaofeng (State Key Laboratory for Agrobiotechnology, China Agricultural University) ;
  • Meng, Qingyong (State Key Laboratory for Agrobiotechnology, China Agricultural University) ;
  • Xu, Guoheng (Peking University Health Science Center) ;
  • Hu, Xiaoxiang (State Key Laboratory for Agrobiotechnology, China Agricultural University) ;
  • Li, Ning (State Key Laboratory for Agrobiotechnology, China Agricultural University)
  • 발행 : 2010.02.28
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초록

Clenbuterol, a $\beta_2$-adrenoceptor agonist, has been proven to be a powerful repartition agent that can decrease fat deposition. Based on results from our previous cDNA microarray experiment of pig clenbuterol administration, a novel up-regulated EST was full-length cloned (4859 bp encoding 1041 amino acids) and found to be the pig homolog of large tumor suppressor 2 (Lats2). We mapped pig Lats2 to chromosome 11p13-14 by using FISH, and western blotting demonstrated that pig Lats2 protein was most abundant in adipose. In Drosophila, Lats2 ortholog was reported as a key component of the Hippo pathway which regulates cell differentiation and growth. Here, we show that pig Lats2 exhibit inverted expression to YAP1, another member of the Hippo pathway which positively regulates cell growth and proliferation, during the differentiation of 3T3-L1 preadipocytes. Our results suggested that Lats2 may involve in Hippo pathway regulating the fat reduction by inhibiting adipocyte differentiation and growth.

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참고문헌

  1. Lafontan, M., Berlan, M. and Prud'Hon, M. (1988) Beta adrenergic agonists. Mechanisms of action: lipid mobilization and anabolism. Reprod. Nutr. Dev. 28, 61-84.
  2. Rule, D. C., Smith, S. B. and Mersmann, H. J. (1987) Effects of adrenergic agonists and insulin on porcine adipose tissue lipid metabolism in vitro. J. Anim. Sci. 65, 136-149. https://doi.org/10.2527/jas1987.651136x
  3. Stoffel, B. and Meyer, H. H. (1993) Effects of the beta-adrenergic agonist clenbuterol in cows: lipid metabolism, milk production, pharmacokinetics, and residues. J. Anim. Sci. 71, 1875-1881. https://doi.org/10.2527/1993.7171875x
  4. Kuiper, H. A., Noordam, M. Y., van Dooren-Flipsen, M. M., Schilt, R. and Roos, A. H. (1998) Illegal use of beta-adrenergic agonists: European Community. J. Anim. Sci. 76, 195-207. https://doi.org/10.2527/1998.761195x
  5. Mitchell, G. A. and Dunnavan, G. (1998) Illegal use of beta-adrenergic agonists in the United States. J. Anim. Sci. 76, 208-211. https://doi.org/10.2527/1998.761208x
  6. Mersmann, H. J. (1998) Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J. Anim. Sci. 76, 160-172. https://doi.org/10.2527/1998.761160x
  7. Zhou, L., Li, Y., Nie, T., Feng, S., Yuan, J., Chen, H. and Yang, Z. (2007) Clenbuterol inhibits SREBP-1c expression by activating CREB1. J. Biochem. Mol. Biol. 40, 525-531. https://doi.org/10.5483/BMBRep.2007.40.4.525
  8. Zhang, J., He, Q., Liu, Q. Y., Guo, W., Deng, X. M., Zhang, W. W., Hu, X. X. and Li, N. (2007) Differential gene expression profile in pig adipose tissue treated with/without clenbuterol. BMC Genomics 8, 433. https://doi.org/10.1186/1471-2164-8-433
  9. Justice, R. W., Zilian, O., Woods, D. F., Noll, M. and Bryant, P. J. (1995) The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 9, 534-546. https://doi.org/10.1101/gad.9.5.534
  10. Xu, T., Wang, W., Zhang, S., Stewart, R. A. and Yu, W. (1995) Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121, 1053-1063.
  11. McPherson, J. P., Tamblyn, L., Elia, A., Migon, E., Shehabeldin, A., Matysiak-Zablocki, E., Lemmers, B., Salmena, L., Hakem, A., Fish, J., Kassam, F., Squire, J., Bruneau, B. G., Hande, M. P. and Hakem, R. (2004) Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J. 23, 3677-3688. https://doi.org/10.1038/sj.emboj.7600371
  12. Yabuta, N., Fujii, T., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Nishiguchi, H., Endo, Y., Toji, S., Tanaka, H., Nishimune, Y. and Nojima, H. (2000) Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts. Genomics 63, 263-270. https://doi.org/10.1006/geno.1999.6065
  13. Pan, D. (2007) Hippo signaling in organ size control. Genes Dev. 21, 886-897. https://doi.org/10.1101/gad.1536007
  14. Huang, J., Wu, S., Barrera, J., Matthews, K. and Pan, D. (2005) The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell 122, 421-434. https://doi.org/10.1016/j.cell.2005.06.007
  15. Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S. A., Gayyed, M. F., Anders, R. A., Maitra, A. and Pan, D. (2007) Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130, 1120-1133. https://doi.org/10.1016/j.cell.2007.07.019
  16. Huang, X. and Madan, A. (1999) CAP3: a DNA sequence assembly program. Genome Res. 9, 868-877. https://doi.org/10.1101/gr.9.9.868
  17. Student, A. K., Hsu, R. Y. and Lane, M. D. (1980) Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes. J. Biol. Chem. 255, 4745-4750.
  18. Green, H. and Kehinde, O. (1979) Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. J. Cell. Physiol. 101, 169-171. https://doi.org/10.1002/jcp.1041010119
  19. Ohsumi, J., Sakakibara, S., Yamaguchi, J., Miyadai, K., Yoshioka, S., Fujiwara, T., Horikoshi, H. and Serizawa, N. (1994) Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells. Endocrinology 135, 2279-2282. https://doi.org/10.1210/en.135.5.2279
  20. Petruschke, T. and Hauner, H. (1993) Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells. J. Clin. Endocrinol. Metab. 76, 742-747. https://doi.org/10.1210/jc.76.3.742
  21. Du, Z., Zhao, D., Zhao, Y., Wang, S., Gao, Y. and Li, N. (2007) Identification and characterization of bovine regulator of telomere length elongation helicase gene (RTEL): molecular cloning, expression distribution, splice variants and DNA methylation profile. BMC. Mol. Biol. 8, 18. https://doi.org/10.1186/1471-2199-8-18
  22. Pi, Y., Liao, Z., Chai, Y., Zeng, H., Wang, P., Gong, Y., Pang, Y., Sun, X. and Tang, K. (2006) Molecular cloning and characterization of a novel stem-specific gene from Camptotheca acuminata. J. Biochem. Mol. Biol. 39, 68-75. https://doi.org/10.5483/BMBRep.2006.39.1.068
  23. Liu, W., Zhao, Y., Liu, Z., Zhang, Y., Lian, Z. and Li, N. (2006) Construction of a 7-fold BAC library and cytogenetic mapping of 10 genes in the giant panda (Ailuropoda melanoleuca). BMC Genomics 7, 294. https://doi.org/10.1186/1471-2164-7-294
  24. Zhang, R., Rao, M., Li, C., Cao, J., Meng, Q., Zheng, M., Wang, M., Dai, Y., Liang, M. and Li, N. (2009) Functional recombinant human anti-HAV antibody expressed in milk of transgenic mice. Transgenic. Res. 18, 445-453. https://doi.org/10.1007/s11248-008-9241-0

피인용 문헌

  1. Lats2 Modulates Adipocyte Proliferation and Differentiation via Hippo Signaling vol.8, pp.8, 2013, https://doi.org/10.1371/journal.pone.0072042
  2. The LATS1 and LATS2 tumor suppressors: beyond the Hippo pathway vol.24, pp.9, 2017, https://doi.org/10.1038/cdd.2017.99
  3. MicroRNA-181b suppresses TAG via target IRS2 and regulating multiple genes in the Hippo pathway vol.348, pp.1, 2016, https://doi.org/10.1016/j.yexcr.2016.09.004
  4. miR-30e-5p and miR-15a Synergistically Regulate Fatty Acid Metabolism in Goat Mammary Epithelial Cells via LRP6 and YAP1 vol.17, pp.11, 2016, https://doi.org/10.3390/ijms17111909
  5. Clenbuterol upregulates histone demethylase JHDM2a via the β2-adrenoceptor/cAMP/PKA/p-CREB signaling pathway vol.24, pp.12, 2012, https://doi.org/10.1016/j.cellsig.2012.07.010